Brain Injury: Signs of Trouble

Gauging the severity of brain trauma could become simpler if scientists can find molecular tip-offs.

The diagnosis of traumatic brain injury still depends largely on observing symptoms and gauging their severity—often an inexact art that may leave questions about which therapies could be most effective. But researchers are working to identify biomarkers—measurable changes in proteins, lipids and other molecular compounds, perhaps detectable in a patient’s blood—that may be more precise. The challenge, says Ross Zafonte, chief of physical medicine and rehabilitation at Massachusetts General Hospital and Spaulding, is to find out which changes are associated with, and perhaps can help predict, recovery from injury.

Several biomarkers hold promise, though this work remains at an early stage. One, called S-100ß—a protein secreted by astrocytes, a type of glial cell in the brain—is thought to correlate with nerve cell injury or death. Two studies have shown that S-100ß blood levels in patients with mild TBI differ from S-100ß levels of those with severe injuries. What’s more, research has consistently shown that patients with lower S-100ß levels may achieve a greater degree of recovery. However, S-100ß is also elevated in trauma patients with bone fractures and skin, muscle or joint injuries who don’t have brain injuries.

Another possible biomarker, ubiquitin C-terminal hydrolase-L1, or UCH-L1, plays a crucial role in removing misfolded, extra and damaged proteins in neurons, so its presence could suggest that it has been recruited in response to a brain injury. The presence in a patient’s blood of a third biomarker, glial fibrillary acidic protein, or GFAP, which forms most of the cytoskeleton—or external structure—of astrocytes, could indicate damage to these cells. And levels of several components produced during the breakdown of a protein found primarily in neurons, called αII-spectrin, may rise if neurons are damaged.

If and when researchers are able to confirm that particular biomarkers are related to specific brain injuries, they could be used to make accurate, quick diagnoses of milder forms of TBI as well as to monitor and evaluate the effectiveness of treatments.